Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas.

The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P= .0008) and the glioblastoma (P= .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] = 1.4, P= .01) and glioblastomas (HR = 1.4, P< .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients.

Longitudinal prospective study of matrix metalloproteinase-9 as a serum marker in gliomas.

The objective of this study was to evaluate if longitudinal measurements of serum matrix metalloproteinase-9 (MMP-9) correlated with disease status or survival in adults with gliomas. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. MMP-9 levels were determined by ELISA and correlated with radiographic disease status and survival. Forty-one patients with low-grade gliomas, 105 with anaplastic gliomas, and 197 with glioblastoma enrolled in this study from August 2002 to September 2008. A total of 1,684 serum samples (97.1% of all MMP-9 samples) had a matching MRI scan. No statistically significant association was observed between levels of serum MMP-9 and radiographic disease status in low-grade gliomas (P = 0.98), anaplastic gliomas (P = 0.39) or glioblastomas (P = 0.33). Among patients with glioblastoma, longitudinal increases in MMP-9 had a weak association with shorter survival (HR = 1.1 per each doubling in MMP-9 levels, 95% CI, 1.0-1.3, P = 0.04) but they were not independently associated with survival when adjusted for age, extent of resection, and performance status. Changes in serum MMP-9 were not associated with survival in the anaplastic glioma cohort. Serum MMP-9 showed no utility in determining glioma disease status and was not a clinically relevant prognostic marker of survival.

A review of methylnaltrexone, a peripheral opioid receptor antagonist, and its role in opioid-induced constipation.

OBJECTIVES: Opioid medications are frequently used in pain and palliative care patients with malignancy to manage symptoms such as pain and dyspnea. However, opiates are associated with various side effects. Constipation is a particularly problematic and common side effect of opioid pharmacology. Opioid antagonists have been studied in the management of opioid-induced constipation. Methylnaltrexone (MNTX) is a peripheral opioid antagonist currently under clinical investigation. It offers the potential to reverse undesirable side effects without reversing analgesia. METHODS: This article attempts to review existing clinical data, focusing on antagonism of opioid-induced adverse effects on the gastrointestinal system. RESULTS: MNTX seems to be well tolerated with limited or transient side effects. MNTX has been shown to improve oral-cecal transit times in opioid treated patients, induce laxation in chronic opioid users, and neither reverses the analgesic effects of morphine nor cause withdrawal symptoms. SIGNIFICANCE OF RESULTS: Larger clinical trials of MNTX are still necessary to support its use as a standard for treatment of opioid-induced constipation.